The present invention relates to the field of pharmacology. More particularly the present invention relates to a hemostatic textile material to stop bleeding and to methods for producing blood-arresting (hemostatic) preparations on a partially oxidized cellulose base.
Hemostatic textile materials are well known. European patent application No. 1,153,620 describes a hemostatic dressing for preventing any bacterial contamination of a wound and made of oxidized cellulose SURGIGEL® (Johnson & Johnson) containing from 1 to 10,000 p.p.m. of ferric ions (Fe3+). European patent application No. 468,114 describes a soluble hemostatic material available as a fabric made of cellulose which has first been oxidized with mono-chloro-acetic acid and sodium hypochlorite to introduce carboxylic groups COOH on to the cellulose substrate. European patent application No. 659,440 describes a method for preparing a hemostatic material on an oxidized cellulose base comprising 0.5 to 4.0% of calcium as well as thrombin, fibrinogen and/or an antifibrinolytic agent.
One of the drawbacks of these known methods is the degree of oxidation of the textile fabric. The use of cellulose, having a low and/or mild degree of oxidation, requiring the conversion of CH2OH groups into carboxylic groups (COOH) results in precluding any possibility of obtaining a material capable of strongly and effectively binding other components thereto. Only calcium ions become bound with COOH— groups with the intermediacy of ionic forces whereas all other components present as a physical (mechanical) mixture.
In laid-open German Patent No. 4000797, C 12N 11/02, Jul. 18, 1991; and GB Patent No. 2,240,040 A, dated Jul. 24, 1991; and Russian Patent No. 2062113, A 61 L 15/38 Jun. 20, 1996, there are mentioned carriers which contain reactive functional groups that are used for preparing materials containing immobilized enzymes having prolonged action for treating wounds and burns.
Known in the art according to U.S. Pat. No. 6,500,799 B2 dated Dec. 31, 2002 is a method for preparing a carrier which comprises aldehyde functional groups having 0.208% w/w-corresponding to 0.026 mg-equiv.- to 0.48 w/w-corresponding to 0.06 mg.-equiv. per gram of carrier, for binding enzymes and other bioactive substances.
Russian Patent No. 2,235,539 describes a method for preparing a powdered material to arrest bleeding, which comprises the stages of mixing, in an aqueous solution, a carrier, i.e., partially oxidized cellulose, with blood coagulation factors, i.e., thrombin and fibrinogen, supplemented with gelatin, ε-aminocaproic acid and lysozyme. Dialdehyde cellulose in the form of a fabric is used as a partially oxidized cellulose having the degree of oxidation (i.e., the content of aldehyde groups) of from 4% to 6%, with the ratios between the components being as follows:
dialdehyde cellulose1g;fibrinogen18-22mg;gelatin27-33mg;ε-aminocaproic acid45-55mg;lysozyme9.5-10.5mg;thrombin350Units; andwater6.5ml.
The components are combined so as to obtain a complete covalent binding of the therapeutic substances with the dialdehyde cellulose. This is followed by drying and grinding to produce a powder. The final product, which contains fibrinogen and thrombin, is disadvantageous due to the premature conversion of the fibrinogen into a fibrin clot through interaction with the thrombin. In such cases the product(s) will be rendered useless.
The known method of U.S. Pat. No. 2,235,539, which describes how to overcome this major problem, has significant shortcomings. The proposed solution is most complicated and utilizes a disjointed production process. In order to prevent thrombin from activating fibrinogen, the preparation is manufactured in two stages. Thus a solution with half of the total amount of water and fibrinogen, ε-aminocaproic acid and a half of the total amount of gelatin is prepared. Half the amount of the dialdehyde cellulose textile fabric is immersed in the above mentioned solution, for 3-4 hours, pressed and air-dried.
A separate solution is prepared that contains the remaining amount of water, thrombin, lysozyme and the remaining amount of gelatin. The remaining dialdehyde cellulose is immersed into this separately prepared solution, for 3-4 hours. The semi-finished products are pressed out, air-dried and ground together for immediate use only.
It is well known that products containing animal or human proteins such as thrombin and fibrinogen, carry the risk of blood-born transmittable agents, especially if these products have not undergone viral inactivation procedures.
In respect to the safety of patients and medical personnel as well, it is a common desire to use preparations, which are free of blood components, thus avoiding the hazard of infection from blood-born transmittable agents.
Furthermore, the dialdehyde textile produced according to the above mentioned patents, because of lack of aldehyde functional groups or functional groups not equally spread, will fail to achieve the goal of covalently binding only 85-90% of the total amino groups into the fabric; so that 10-15% of gelatin and tranexamic acid or ε-aminocaproic acid, chitosan, lysozyme and/or other antimicrobial ingredients as described hereinbefore, can be adsorbed on the carrier so as to ensure the presence of a sufficient quantity thereof for arresting severe and fast bleeding, and for stabilizing the clotting, and avoiding fibrinolysis, as proposed by the present invention.